Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder which manifests with insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Homozygous or compound heterozygous mutations in four genes are associated with the four subtypes of CGL. The condition appears in early childhood with accelerated linear growth, quick aging of bones, and a large appetite. As the child grows up, acanthosis nigricans (hyperpigmentation and thickening of skin) will begin to present itself throughout the body – mainly in the neck, trunk, and groin. The disorder also has characteristic features like hepatomegaly or an enlarged liver which arises from fatty liver and may lead to cirrhosis, muscle hypertrophy, lack of adipose tissue, splenomegaly, hirsutism (excessive hairiness) and hypertriglyceridemia. Fatty liver and muscle hypertrophy arise from the fact that lipids are instead stored in these areas; whereas in a healthy individual, lipids are distributed more uniformly throughout the body subcutaneously. The absence of adipose tissue where they normally occur causes the body to store fat in the remaining areas. Common cardiovascular problems related to this syndrome are cardiac hypertrophy and arterial hypertension (high blood pressure). This disorder can also cause metabolic syndrome. Most with the disorder also have a prominent umbilicus or umbilical hernia. Commonly, patients will also have acromegaly with enlargement of the hands, feet, and jaw. After puberty, additional symptoms can develop. In women, clitoromegaly and polycystic ovary syndrome can develop. This impairs fertility for women, and only a few documented cases of successful pregnancies in women with CGL exist. However, the fertility of men with the disorder is unaffected.

The presentation of this condition includes a characteristic facies. The cardiac manifestations include patent ductus arteriosus, congenital hypertrophy of the left ventricle, and pericardial effusions.

Neurodevelopmental outcome appears normal, but obsessive traits and anxiety have been reported. It may also be associated with recurrent infections with low immunoglobulin levels and gastric bleeding, and additional possible associations include lymphoedema and heterochromia iridis.

There are differences in how Type 1 vs Type 2 patients are affected by the disease. In type 1 patients, they still have mechanical adipose tissue, but type 2 patients do not have any adipose tissue, including mechanical. In type 2 patients, there is a greater likelihood of psychomotor retardation and intellectual impairment.

Familial partial lipodystrophy (FPL), also known as Köbberling–Dunnigan syndrome, is a rare genetic metabolic condition characterized by the loss of subcutaneous fat.

FPL also refers to a rare metabolic condition in which there is a loss of subcutaneous fat in the arms, legs and lower torso. The upper section of the body, face, neck, shoulders, back and trunk carry an excess amount of fat.

As the body is unable to store fat correctly this leads to fat around all the vital organs and in the blood (triglycerides). This results in heart problems, cirrhosis of the liver, lipoatrophic diabetes, and pancreatitis, along with various other complications.

Cantú syndrome (hypertrychotic osteochondrodysplasia) is a rare condition characterized by hypertrichosis, osteochondrodysplasia, and cardiomegaly. Less than 50 cases have been described in the literature; they are associated with a mutation in the "ABCC9"-gene that codes for the ABCC9-protein.

Acquired generalized lipodystrophy (also known as "Lawrence syndrome," and "Lawrence–Seip syndrome", abbreviation: AGL) is a rare skin condition that appears during childhood or adolescence, characterized by fat loss affecting large areas of the body, particularly the face, arms, and legs. There are 4 types of lipodystrophy based on its onset and areas affected: acquired or inherited (congenital or familial), and generalized or partial. Both acquired or inherited lipodystrophy present as loss of adipose tissues. The near-total loss of subcutaneous adipose tissue is termed generalized lipodystrophy while the selective loss of adipose tissues is denoted as partial lipodystrophy. Thus, as the name suggests, AGL is a near-total deficiency of adipose tissues in the body that is developed later in life. It is an extremely rare disease that only about 100 cases are reported worldwide. There are three main etiologies of AGL suspected: autoimmune, panniculitis-associated, or idiopathic. After its onset, the disease progresses over a few days, weeks, months, or even in years. Clinical presentations of AGL are similar to other lipodystrophies, including metabolic complications and hypoleptinemia. Treatments are also similar and mainly supportive for symptomatic alleviation. Although HIV- or drug-induced lipodystrophy are a type of acquired lipodystrophy, its origin is very specific and distinct hence is usually not discussed with AGL (see HIV-Associated Lipodystrophy).

Dunnigan-type familial partial lipodystrophy, also known as FPLD Type II and abbreviated as (FPLD2), is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes usually type 2, dyslipidemia, hypertension, and early endpoints of atherosclerosis. It can also result in hepatic steatosis. FPLD results from mutations in LMNA gene, which is the gene that encodes nuclear lamins A and C.

Appearance at birth and during the early years is normal but features become more prominent during later childhood prior to puberty. The main issues appear to be lipodystrophy (see below) and slow growth of cartilage and ligaments. The slow growth of cartilage and ligaments results in a small nose, small mandible (jaw), small ears and tightening of ligaments in the limbs. A small larynx (due to

the reduced growth of cartilage) can mean the voice is likely to remain high pitched (even in boys after puberty).

Lipodystrophy can be divided into the following types:

- Congenital lipodystrophies

- Congenital generalized lipodystrophy (Beradinelli-Seip syndrome)

- Familial partial lipodystrophy

- Marfanoid–progeroid–lipodystrophy syndrome

- Acquired lipodystrophy

- Acquired partial lipodystrophy (Barraquer-Simons syndrome)

- Acquired generalized lipodystrophy

- Centrifugal abdominal lipodystrophy (Lipodystrophia centrifugalis abdominalis infantilis)

- Lipoatrophia annularis (Ferreira-Marques lipoatrophia)

- Localized lipodystrophy

- HIV-associated lipodystrophy

Lipodystrophy is a disorder in which the body is unable to produce fat. The medical condition is characterized by abnormal or degenerative conditions of the body's adipose tissue. ("Lipo" is Greek for "fat", and "dystrophy" is Greek for "abnormal or degenerative condition".) A more specific term, "lipoatrophy", is used when describing the loss of fat from one area (usually the face). This condition is also characterized by a lack of circulating leptin which may lead to osteosclerosis.

Wiedemann–Rautenstrauch (WR) syndrome , also known as neonatal progeroid syndrome, is an autosomal recessive progeroid syndrome.

WR was first reported by Rautenstrauch and Snigula in 1977; and the earliest reports made subsequently have been by Wiedemann in 1979, by Devos in 1981, and Rudin in 1988. There have been over 30 cases of WR.

WR is associated with abnormalities in bone maturation, and lipids and hormone metabolism. Affected individuals exhibit intrauterine and postnatal growth retardation, leading to short stature and an aged appearance from birth. They have physical abnormalities including a large head (macrocephaly), sparse hair, prominent scalp veins, inward-folded eyelid (entropion), widened anterior fontanelles, hollow cheeks (malar hypoplasia), general loss of fat tissues under the skin (lipoatrophy), delayed tooth eruption, abnormal hair pattern (hypotrichosis), beaked nose, mild to severe mental retardation and dysmorphism.

Marfan lipodystrophy syndrome (MFLS) has sometimes been confused with Wiedemann–Rautenstrauch syndrome, since the Marfanoid features are progressive and sometimes incomplete. MFLS is caused by mutations near the 3'-terminus of "FBN1" that cause a deficiency of the protein hormone asprosin and progeroid-like symptoms with reduced subcutaneous white adipose tissue.

The clinical presentation is similar to people with congenital lipodystrophy: the only difference is that AGL patients are born with normal fat distribution and symptoms develop in childhood and adolescence years and rarely begins after 30 years of age. Females are more often affected than males, with ratio being 3:1.

The hallmark characteristics are widespread loss of subcutaneous fat, ectopic fat deposition, leptin deficiency, and severe metabolic abnormalities such as insulin resistance. Subcutaneous fat loss in AGL patients are visible in all parts of the body. AGL mostly affects face and the extremities and may look sunken or swollen in the eyes. However, the degree and location of severity may vary by person. Especially, intra-abdominal fat loss is variable. As subcutaneous fat is lost, affected areas show prominent structures of veins and muscle. Those with panniculitis-associated AGL may present erythematous nodules.

Metabolic complications include insulin resistance, high metabolic rate, and uncontrolled lipid levels such as hypertriglyceridemia, low HDL, and high LDL. Patients may develop diabetes mellitus secondary to insulin resistance.

Recent case reports reveled that lymphoma is present in some patients but its prevalence is not known at this time.

The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features ("e.g.," inverted nipples and subcutaneous fat pads; and strabismus. If an MRI is obtained, cerebellar atrophy and hypoplasia is a common finding.

Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic disc pallor, and reduced rod function on electroretinography.

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

SHORT is an acronym for short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, rieger anomaly and teething delay.

Other characteristics common in SHORT syndrome are a triangular face, small chin with a dimple, a loss of fat under the skin (lipodystrophy), abnormal position of the ears, hearing loss and delayed speech.

This condition is characterised by symmetrical lesions on the temples resembling forceps marks. It is characterized a puckered skin due to a virtual absence of subcutaneous fat. It is apparent at birth. Other lesions that may be present include puffy, wrinkled skin around the eyes and/or abnormalities of the eyelashes, eyebrows, and eyelids. The eyebrows may be up slanting or outward slanting. Occasionally the bridge of the nose may appear flat, while the tip may appear unusually rounded. The chin may be furrowed. The upper lip may be prominent with a down turned mouth. Other features that have been reported include dysplastic and low set ears, linear radiatory impressions on the forehead and congenital horizontal nystagmus.

Those with the Setleis syndrome may be missing eyelashes on both the upper and lower lids or may have multiple rows of lashes on the upper lids but none on the lower lids.A possible association with intra abdominal cancer has been reported but to date this has not been confirmed in other studies.

The diagnosis of MDP syndrome is suggested by the clinical features. It can be confirmed by finding a mutation in the POLD1 gene, a service offered by the molecular genetics team at the Royal Devon and Exeter NHS Foundation Trust / Exeter University who originally discovered the genetic cause.

Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as Marfan lipodystrophy syndrome (MFLS) or progeroid fibrillinopathy, is an extremely rare medical condition which manifests as a variety of symptoms including those usually associated with Marfan syndrome, an appearance resembling that seen in neonatal progeroid syndrome (NPS; also known as Wiedemann–Rautenstrauch syndrome), and severe partial lipodystrophy. It is a genetic condition that is caused by mutations in the "FBN1" gene, which encodes profibrillin, and affects the cleavage products of profibrillin, fibrillin-1, a fibrous structural protein, and asprosin, a glucogenic protein hormone. As of 2016, fewer than 10 cases of the condition have been reported. Lizzie Velasquez and Abby Solomon have become known publicly through the media for having the condition.

In addition to severe lipodystrophy (loss of adipose tissue), individuals with MPL show a concomitant marked loss of lean tissue mass, which also contributes to their "skinny" appearance. Based on visual inspection, it was originally thought that the lipodystrophy associated with MPL was generalized. However, it appears in fact to be partial, being confined to the face, distal extremities, and the and lateral regions of the buttocks. Normal amounts of subcutaneous fat are found in the torso over the chest and abdomen. As such, the breasts are normal in females with MPL.

Individuals with MPL have an appearance of being prematurely aged, but this is not due to actual early aging and is instead due to their paucity of subcutaneous fat. As such, MPL is not truly a form of progeria.

In 2016, it was discovered that the partial lipodystrophy associated with MPL is caused by loss of the C-terminal domain cleavage product of profibrillin and novel glucogenic protein hormone, which has been named asprosin. Due to asprosin deficiency, individuals with MPL eat less, and do not gain weight or develop symptoms of diabetes like insulin resistance. MPL patients burn less energy than normal individuals, but also consume less, and their net energy balance is moderately reduced. In contrast to MPL patients, whose asprosin is undetectable in the blood, individuals with obesity and diabetes have elevated levels of asprosin. As such, "FBN1" has been nicknamed the "thin gene", and drug development for targeted inhibition of asprosin signaling is considered to be an "unusually promising" potential therapeutic route in the treatment of obesity and diabetes.

HIV-associated lipodystrophy commonly presents with fat loss in face, buttocks, arms and legs.

There is also fat "accumulation" in various body parts. Patients often present with "buffalo hump"-like fat deposits in their upper backs. Breast size of patients (both male and female) tends to increase. In addition, patients develop abdominal obesity.

Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild). The subtypes are numbered one to six according to the genetic cause, in the following order: (1) POMT1, (2) POMT2, (3) POMGNT1, (4) FKTN, (5) FKRP, and (6) LARGE.

Most common severe types include:

Keppen–Lubinsky syndrome (KPLBS) is an extremely rare congenital disorder.The minimal clinical criteria for the Keppen–Lubinsky syndrome are as follows: normal growth parameters at birth, postnatal growth failure, peculiar face with an aged appearance (large prominent eyes, a narrow nasal bridge, a tented upper lip, a high palate, an open mouth), skin tightly adherent to facial bones, generalized lipodystrophy, microcephaly, and development delay. Keppen-Lubinsky syndrome is caused by mutation in the inwardly rectifying K+ channels encoded by KCNJ6 gene.

HIV-associated lipodystrophy, also known as lipodystrophy in HIV-infected patients (LD-HIV), is a condition characterized by loss of subcutaneous fat associated with infection with HIV.

Qazi–Markouizos syndrome is a rare hereditary condition characterized by non-progressive, congenital hypotonia, severe intellectual disability, an increased proportion of type 2 muscle fibers, which additionally exhibited increased size, as well as dysharmonic skeletal maturation. To date, the molecular mechanism of Qazi–Markouizos syndrome, which is also known as Puerto Rican infant hypotonia syndrome, remains unknown.

Focal facial dermal dysplasia (FFDD) is a rare genetically heterogeneous group of disorders that are characterized by congenital bilateral scar like facial lesions, with or without associated facial anomalies. It is characterized by hairless lesions with fingerprint like puckering of the skin, especially at the temples, due to alternating bands of dermal and epidermal atrophy.

This condition is also known as Brauer syndrome (hereditary symmetrical aplastic nevi of temples, bitemporal aplasia cutis congenita, bitemporal aplasia cutis congenita: OMIM ) and Setleis syndrome (facial ectodermal dysplasia: OMIM ).

SHORT syndrome is a medical condition in which affected individuals have multiple birth defects in different organ systems.

It was characterized in 1975.

"Maturity onset diabetes of the young" (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. MODY is often referred to as "monogenic diabetes" to distinguish it from the more common types of diabetes (especially type 1 and type 2), which involve more complex combinations of causes involving multiple genes and environmental factors. MODY 2 and MODY 3 are the most common forms. MODY should not be confused with latent autoimmune diabetes of adults (LADA) — a form of type 1 DM, with slower progression to insulin dependence than child-onset type 1 DM, and which occurs later in life.